Effects of Bojungikgitang-gagambang on Longitudinal Bone Growth in Adolescent Rats

  • Lee, Min-Su (Department of Herbal Pharmacology, College of Oriental Medicine, Kyung Hee University) ;
  • Kim, Ji-Young (Department of Herbal Pharmacology, College of Oriental Medicine, Kyung Hee University) ;
  • Kim, Mi-Yeon (Department of Herbal Pharmacology, College of Oriental Medicine, Kyung Hee University) ;
  • Chang, Gyu-Tae (Department of Pediatrics, College of Oriental Medicine, Kyung Hee University) ;
  • Kim, Ho-Cheol (Department of Herbal Pharmacology, College of Oriental Medicine, Kyung Hee University)
  • Received : 2012.01.10
  • Accepted : 2012.05.09
  • Published : 2012.06.30

Abstract

Objectives: This study was aimed to investigate the effect of Bojungikgitang-gagambang (BJIG) on longitudinal bone growth in rats. Methods: The BJIG treated group (300 mg/kg) and the control group (vehicle) were administered orally twice daily for 4 days. To investigate the effects of BJIG we measured body weight gain. The bone growth effect was analyzed by measuring between fluorescent lines marked with tetracycline, which plays the role of fluorescent dye on the surface of the tibia. Tetracycline was intraperitoneally injected. The height of growth plates in the epiphyseal plate was measured. The expression of bone morphogenetic protein-2 (BMP-2) and insuline-like growth factor-1 (IGF-1) was investigated by immunohistochemistry. Results: BJIG caused a significant acceleration of longitudinal bone growth of $349.7{\pm}15.9{\mu}m/day$ compared to control ($319.8{\pm}21.4{\mu}m/day$). The height of overall growth plate was not significantly more compared to the control, but the size of cells in the proliferative zone and hypertrophic zone were. In the immunohistochemistry, BMP-2 and IGF-1 were expressed markedly in the proliferative or hypertrophic zone, respectively. Conclusions: BJIG stimulated the chondrocyte hypertrophy and chondrogenesis in the growth plate and directly increased the longitudinal tibia length of rats.

Keywords

References

  1. Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL et al., 2007 ISS Consensus Workshop participants. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: A summary of the growth hormone research society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology workshop. J Clin Endocrinol Metab. 2008;93(11):4210-4217. https://doi.org/10.1210/jc.2008-0509
  2. Kelnar CJ. Idiopathic short stature: Considerations from the clinic-the viewpoint of the paediatric endocrinologist. Horm Res Paediatr. 2011;76 Suppl 3:35-37.
  3. Wit JM, Reiter EO, Ross JL, Saenger PH, Savage MO, Rogol AD et al., Idiopathic short stature: Management and growth hormone treatment. Growth Horm IGF Res. 2008;18(2):111-135. https://doi.org/10.1016/j.ghir.2007.11.003
  4. Leem K, Park SY, Lee DH, Boo YM, Cho KH, Lim J et al., Effects of jaoga-yukmiwon(R), a Korean herbal medicine, on chondrocyte proliferation and longitudinal bone growth in adolescent male rats. Phytother Res. 2003;17(9):1113-1116. https://doi.org/10.1002/ptr.1321
  5. Kim MY, Park Y, Pandit NR, Kim J, Song M, Park J et al., The herbal formula HT042 induces longitudinal bone growth in adolescent female rats. J Med Food. 2010;13(6): 1376-1384. https://doi.org/10.1089/jmf.2010.1007
  6. Harada M, Seta K, Ito O, Tamada K, Li T, Terao H et al., Concomitant immunity against tumor development is enhanced by the oral administration of a Kampo medicine, hochu-ekki-to(TJ-41: Bu-zhong-yi-qi-tang). Immunopharmacol Immunotoxicol. 1995;17(4):687-703. https://doi.org/10.3109/08923979509037189
  7. Ito H, Shimura K. Studies on the antitumor activity of traditional Chinese medicines. (1). Gan To Kagaku Ryoho. 1985;12(11):2145-2148.
  8. Jeong JS, Ryu BH, Kim JS, Park JW, Choi WC, Yoon SW. Bojungikki-tang for cancer-related fatigue: A pilot randomized clinical trial. Integr Cancer Ther. 2010;9(4):331-338. https://doi.org/10.1177/1534735410383170
  9. Kim SH, Lee SE, Oh H, Kim SR, Yee ST, Yu YB et al., The radioprotective effects of bu-zhong-yi-qi-tang: A prescription of traditional Chinese medicine. Am J Chin Med. 2002;30(1):127-137. https://doi.org/10.1142/S0192415X02000144
  10. Yan X, Kita M, Minami M, Yamamoto T, Kuriyama H, Ohno T et al., Antibacterial effect of Kampo herbal formulation hochu-ekki-to (buzhong- yi-qi-tang) on helicobacter pylori infection in mice. Microbiol Immunol. 2002;46(7):475-482. https://doi.org/10.1111/j.1348-0421.2002.tb02721.x
  11. Koshikawa N, Imai T, Takahashi I, Yamauchi M, Sawada S, Kansaku A. Effects of hochu-ekki-to, yoku-kan-san and saiko-ka-ryukotsu-borei-to on behavioral despair and acetic acid-induced writhing in mice. Methods Find Exp Clin Pharmacol. 1998;20(1):47-51. https://doi.org/10.1358/mf.1998.20.1.485631
  12. Ikeda S, Kaneko M, Kumazawa Y, Nishimura C. Protective activities of a Chinese medicine, hochu-ekki-to, to impairment of hematopoietic organs and to microbial infection. Yakugaku Zasshi. 1990;110(9):682-687. https://doi.org/10.1248/yakushi1947.110.9_682
  13. Ishikawa H, Manabe F, Zhongtao H, Yoshii S, Koiso K. The hormonal response to HCG stimulation in patients with male infertility before and after treatment with hochuekkito. Am J Chin Med. 1992;20(2):157-165. https://doi.org/10.1142/S0192415X92000163
  14. De Luca F, Barnes KM, Uyeda JA, De-Levi S, Abad V, Palese T et al., Regulation of growth plate chondrogenesis by bone morpho- genetic protein-2. Endocrinology. 2001;142(1): 430-436. https://doi.org/10.1210/en.142.1.430
  15. Hunziker EB. Mechanism of longitudinal bone growth and its regulation by growth plate chondrocytes. Microsc Res Tech. 1994;28(6): 505-519. https://doi.org/10.1002/jemt.1070280606
  16. Iannotti JP. Growth plate physiology and pathology. Orthop Clin North Am. 1990;21(1): 1-17.
  17. Yoshizato H, Fujikawa T, Shibata M, Tanaka M, Nakashima K. Stimulation of growth hormone gene expression in the pituitary and brain by panax ginseng C. A. MEYER. Endocr J. 1999;46 Suppl:S85-S88. https://doi.org/10.1507/endocrj.46.Suppl_S85
  18. Liu HJ, Wang XP, Lin J, Yu YC, Jiang XQ, Zhang XL et al., Zhou ZT, Zhang WD. The effect of icariin and astragalosid I on the proliferation and differentiation of bone marrow stromal cells. Zhong Yao Cai. 2006;29(10):1062-1065.
  19. Kim C, Ha H, Kim JS, Kim YT, Kwon SC, Park SW. Induction of growth hormone by the roots of astragalus membranaceus in pituitary cell culture. Arch Pharm Res. 2003;26(1):34-39. https://doi.org/10.1007/BF03179928
  20. Demerath EW, Jones LL, Hawley NL, Norris SA, Pettifor JM, Duren D et al., Rapid infant weight gain and advanced skeletal maturation in childhood. J Pediatr. 2009;155(3):355-361. https://doi.org/10.1016/j.jpeds.2009.03.016
  21. Hutchison MR, Bassett MH, White PC. Insulin-like growth factor-I and fibroblast growth factor, but not growth hormone, affect growth plate chondrocyte proliferation. Endocrinology. 2007; 148(7):3122-3130. https://doi.org/10.1210/en.2006-1264
  22. Robson H. Bone growth mechanisms and the effects of cytotoxic drugs. Arch Dis Child. 1999;81(4):360-364. https://doi.org/10.1136/adc.81.4.360
  23. De Luca F. Impaired growth plate chondrogenesis in children with chronic illnesses. Pediatr Res. 2006;59(5):625-629. https://doi.org/10.1203/01.pdr.0000214966.60416.1b
  24. Mackie EJ, Tatarczuch L, Mirams M. The skeleton: A multi-functional complex organ. The growth plate chondrocyte and endochondral ossification. J Endocrinol. 2011;211(2):109-121. https://doi.org/10.1530/JOE-11-0048
  25. Urist MR. Bone: Formation by autoinduction. Science. 1965;150(698):893-899. https://doi.org/10.1126/science.150.3698.893
  26. Wozney JM, Rosen V. Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin Orthop Relat Res. 1998;(346)(346):26-37.
  27. Huang Y, Kim SO, Yang N, Jiang J, Frank SJ. Physical and functional interaction of growth hormone and insulin-like growth factor-I signaling elements. Mol Endocrinol. 2004;18(6): 1471-1485. https://doi.org/10.1210/me.2003-0418
  28. Wang J, Zhou J, Cheng CM, Kopchick JJ, Bondy CA. Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth. J Endocrinol. 2004; 180(2):247-255. https://doi.org/10.1677/joe.0.1800247